Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1   Pharmacodynamic properties
Pharmacotherapeutic group: Retinoids for topical use in acne.
ATC Code: D10AD01


The precise mechanism of action of tretinoin in the treatment of acne is not known. However, biochemical and pharmacological profile studies have clearly demonstrated that tretinoin is a potent modulator of cellular differentiation and keratinisation processes which are abnormally present in the pathology of acne vulgaris.

RET-AVIT has been investigated in a total of 960 patients. Of these, 674 patients were included in two large randomised, placebo (vehicle) controlled, investigator blinded studies of safety and efficacy. These studies were of 12 weeks duration and included male and female mild to moderate acne vulgaris patients from 10 to 65 years of age.

In the two clinical studies described above, RET-AVIT was shown to be significantly more effective than its vehicle in reducing both inflammatory and non-inflammatory lesions associated with acne vulgaris. For the combined study populations, at 12 weeks RET-AVIT produced a mean percentage reduction in inflammatory and noninflammatory acne lesions of 33.2% and 38.9%, respectively, compared to 18.4% and 19.7%, respectively, for vehicle (p < 0.001). The analysis of the dichotomized global severity score at Week 12 resulted in a significant treatment effect in favour of RET-AVIT, compared to its vehicle (p=0.002).

The adverse event profile observed in the studies was consistent with the known profile for topical tretinoin products – See section 4.8.

Relapse rates following treatment of acne with topical tretinoin have not been studied.

Pharmacokinetic Properties

5.2   Pharmacokinetic properties

Tretinoin is a metabolite of Vitamin A. Systemic absorption was evaluated in a total of twenty-eight male and female acne patients, 13 to 37 years of age. The plasma concentrations of tretinoin and its metabolites, 13-cis- retinoic acid and 4-oxo-13- cisretinoic acid, ranged from 0.6 to 6.2 ng/mL and were essentially unaltered after fourteen daily applications of 4 g daily doses of RET-AVIT, relative to baseline levels.


In a Phase III twelve-week study of 936 acne patients, the plasma concentrations of tretinoin and its metabolites, 13-cis-retinoic acid and 4-oxo- 13-cis-retinoic acid were evaluated at Baseline and Week 12. The plasma concentrations of tretinoin and its metabolites, 13-cis-retinoic acid and 4-oxo- 13-cis-retinoic acid, ranged from 0.5 to
5.3 ng/mL and were essentially unaltered after twelve weeks of daily application of RET-AVIT.